Microcapsules containing an oxidizable active, and a process for preparing the same

ABSTRACT

Disclosed is a microcapsule including a core having an oxidizable active (OA), the outer part of said core being in a solid form, and a water insoluble coating obtained from an encapsulating agent (EA), with the coating surrounding said core. In particular, the EA can be water soluble or organic solvent soluble, in particular in ethanol. The microcapsule can also include an EA in which the water solubility is pH-dependent. Also, the core does not contain a metal oxide, and the coating does not include a disintegrant, such as sodium starch glycolate. Also disclosed is a process for preparing the microcapsules.

FIELD OF THE INVENTION

The present invention relates to microcapsules containing an oxidizableactive, and a process for preparing the same.

BACKGROUND OF THE INVENTION

There is an increasing need in the industry, for example in the food,pharmaceutical or cosmetics industry, for protection of active agentsfrom the medium that surrounds said active agents in particular toachieve a better conservation of said active agents.

One of the main issues of encapsulation is to be able to protect drugsfrom external medium but also to allow the right release or the rightaccess to this drug when needed. This access is very often possiblethrough a quick or controlled release in the medium, due to chosenproperties of the encapsulating agent.

This dual aim of protection and release becomes more complex as soon asexchanges between drugs and medium need to be kept out of directinteractions in-between drug and external medium. S. K. Tam and al. haveshown (in Vandamme et al Microeneapsulation; Tec & Doc; 2007; Chapter11) these issues when the microencapsulation aims to allow therapeuticeffects through useful component exchanges, components which are able tocross the microencapsulation barriers while preserving drugs from beingin direct contact with other potentially damaging components, if theyhad entered the microcapsule.

In case of oxidizable drugs, the issue is to be able to getmicrocapsules which are able to protect these drugs from oxidation, andto protect the external medium from component issued from oxidation ofsaid drugs.

Different kind of encapsulating agents can target this type ofprotection, but polysaccharides are the most often used. They are mainlyused under bead forms containing solutions and cross-linked in salt orcations solutions. Such beads are then stored in wet forms assuspensions particles in solutions.

Chen and al. Journal of Controlled Release 2004, 96, 285-300 reportedthat such beads of polysaccharides can protect bioactive molecules fromharsh acidic conditions such as stomach environment. But no works seemto have been made on the use of such a protection of the external mediumfrom oxidizable agents which could decompose media components.

Moreover, the use of such polysaccharides is mainly achieved withcross-linking through dropping of aqueous solutions containing saidpolysaccharides into aqueous solutions containing salts.

However, the obtained beads suffer several drawbacks: they are mainlystored in aqueous solution, rendering their handling difficult, theirproduction and their transportation expensive. In addition, said beadscannot be used directly in powder preparation, in particular food powdercompositions, or in tablets, in particular for pharmaceutical uses.

No studies have been made on powder microcapsules allowing dry forms ofdrua protections through process avoiding aqueous solution to create theinsoluble external protection of the microcapsule.

SUMMARY OF THE INVENTION

Thus, one aim of the present invention is on the one hand to encapsulateoxidizable active products to protect the media from their action, andon the other hand to implement new processes allowing the manufacture ofthese microcapsules with no absolute need to submerge the microcapsulesin a cross linking bath of an aqueous salt solution.

Another aim of the present invention is to provide microcapsules able toprotect an active from oxidation by a given alimentary, cosmetically orpharmaceutically acceptable medium in which said microcapsules areplaced.

Another aim of the present invention is to provide microcapsules able toprotect the alimentary, cosmetically or pharmaceutically acceptablemedium in which said microcapsules are placed from the active containedin said microcapsules.

Thus, the present invention relates to a microcapsule consisting in orcontaining:

-   -   a core consisting in or comprising an oxidizable active (OA),        and    -   a water insoluble coating obtained from an encapsulating agent        (EA), said coating surrounding said core.

By microcapsule is meant a particle with a size from 1 μm to a 3 mm,comprising an external coating that isolates an encapsulated core fromthe external medium.

By core is meant the material inside the microcapsule.

By coating is meant the wall surrounding the core of said microcapsule.

By “water insoluble coating” is meant a coating, the water solubility ofwhich is low enough to prevent said active to be released from themicrocapsule, when said microcapsule is placed in an aqueous-basedalimentary, cosmetically or pharmaceutically acceptable medium.

The insolubilization of a microcapsule, and thus the fact that saidcoating prevents said active to be released front said microcapsule isfor example determined by the measurement of particle size in water, forinstance with a laser particle sizer.

By “prevent said active to be released from the microcapsule” is meantthat, when said microcapsule is placed in said medium, the concentrationof active in the medium surrounding said microcapsule is below 5% inweight at 25° C., in particular below 1% in weight at 25° C.

By “oxidizable active” is meant an active that is capable of beingoxidized.

By “active being oxidized” is meant a reducing agent oxidized by havingits electrons taken away.

The tendency of an active of having its electrons taken away and therebybe oxidized is in particular measured by its redox potential, as knownby those skilled in the art: an active is likely to be oxidized by anelement of the external medium if the redox potential of said element issuperior to the redox potential of said active.

By “encapsulation agent” is meant a water insoluble agent constitutingsaid water insoluble coating, or a water soluble or organic solvent, inparticular ethanol, soluble agent forming said water insoluble coatingafter a modification of its chemical state.

Two cases can thus be distinguished regarding said water soluble ororganic solvent-soluble agent:

-   -   the first one corresponds to a water soluble agent forming said        water insoluble coating after a modification of its chemical        state;    -   the second one corresponds to a water soluble and organic        solvent, in particular ethanol, soluble agent forming said water        insoluble coating after a modification of its chemical state.

The term “modification of its chemical state” means in particular achemical reaction or a pH modification.

The present invention also relates to a microcapsule consisting in orcontaining:

-   -   a core consisting in or comprising an oxidizable active (OA),        the outer part of said core being in a solid form, and    -   a water insoluble coating obtained from an encapsulating agent        (EA), said coating surrounding said core,    -   with the proviso that:    -   said core does not consist in or comprise a metal oxide, and    -   said coating does not comprise a disintegyant, in particular        sodium starch glycolate.

By “outer part” is meant the part of said core which is in contact withsaid coating.

By “solid form” is meant a crystalline, semi-crystalline or amorphousstate,

In an advantageous embodiment, the present invention relates to amicrocapsule, wherein said core is under solid form.

In a particularly advantageous embodiment, the present invention relatesto a microcapsule, wherein said core is crystalline. In this case, saidoxidizable active is necessarily crystalline.

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is crystalline and solid,i.e. without any space or air cavities.

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is crystalline and containsat least one space or air cavity.

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is crystalline and has awater content less than 10%, in particular less than 6%, by weight.

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is under solid form andamorphous.

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is amorphous and containsat least one space or air cavity, said core being in particular obtainedby spray drying,

In another particularly advantageous embodiment, the present inventionrelates to a microcapsule, wherein said core is amorphous and has awater content less than 10%, in particular less than 6%, by weight.

In an advantageous embodiment, the present invention relates to amicrocapsule, wherein the inner part of said core contains theoxidizable active (OA), said OA being in a liquid form, in particular inan oily form, or in a viscous oil form, or in a pasty form.

In a particularly advantageous embodiment, the present invention relatesto a microcapsule, wherein said inner part of said core is a solidcomprising the OA in a liquid form, in particular in an oily form, or ina viscous oil form, or in a pasty form.

In an advantageous embodiment, the present invention relates to amicrocapsule, wherein said core does not consist in or comprisephospholipids.

In an advantageous embodiment, the present invention relates to amicrocapsule consisting in:

-   -   a single core consisting in or comprising an oxidizable active        (OA) under solid form, and    -   a single water insoluble coating obtained from an encapsulating        agent (EA), said coating surrounding said core.

By <<single core>> is meant a core forming a single and continuousvolume inside said microcapsule.

By “single coating” is meant that said single core is surrounded by asingle wall separating said core from the outside.

In an advantageous embodiment, the present invention relates to amicrocapsule, wherein said oxidizable agent does not belong tocarotenoids.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein the totality of said OA is found in said core.

In an advantageous embodiment, the present invention relates to amicrocapsule consisting in or containing:

-   -   a core consisting in or comprising an oxidizable active (OA),        and    -   a water insoluble coating obtained from an encapsulating agent        (EA), said coating surrounding said core,

providing said microcapsule is placed in an external medium that do notcomprise said OA.

In an advantageous embodiment, the present invention relates to amicrocapsule consisting in or containing:

-   -   a core consisting in or comprising an oxidizable active (OA),        and    -   a water insoluble coating obtained from an encapsulating agent        (EA), said coating surrounding said core,        providing said microcapsule is placed in an external medium that        do not comprise vitamin C or a chemical derivative of vitamin C.

In an advantageous embodiment, the present invention relates to amicrocapsule comprising less than 10%, in particular less than 6%, inweight of water.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is water soluble.

By “water soluble EA” is meant an EA that is sufficiently soluble inwater to form a clear solution to the naked eye at a concentration of 5%in weight in water at 25° C.

By “water insoluble EA” is meant an EA that is sufficiently insoluble inwater to form a turbid solution to the naked eye at a concentration of 1to 5% in weight in water at 25° C.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is organic solvent, in particular ethanol,soluble.

By “organic solvent, in particular ethanol, soluble EA” is meant an EAthat is sufficiently soluble in said solvent, in particular ethanol, toform a clear solution to the naked eye at a concentration of 5% inweight in said solvent at 25° C.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is an agent, the water solubility of whichis pH-dependent.

By “an agent, the water solubility of which is pH-dependent” is meantthat there is at least one pH value for which said agent is watersoluble and at least one pH value for which said agent is waterinsoluble.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water insoluble coating results from thereaction of a water soluble EA with means for inducing waterinsolubility of said EA.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water insoluble coating results from thereaction of an organic solvent, in particular ethanol, soluble EA withmeans for inducing water insolubility of said EA.

By “means for inducing water insolubility” is meant any means thatmodify the chemical state of said water soluble or organic solvent, inparticular ethanol, soluble EA, providing a species that is waterinsoluble in standard reference conditions of temperature and pressurecorresponding to a temperature of 25° C. and a pressure of 100 KPa.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said means for inducing water insolubility are anagent chemically reacting with said EA.

Said means react with said water soluble or organic solvent, inparticular ethanol, soluble EA, providing a water insoluble species.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said means for inducing water insolubility are anacid, abase, or a buffer.

Said acid, base, of buffer brings the pH from a value for which said EAis water soluble to a value for which said EA is water insoluble.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said means for inducing water insolubility consistin the drying of said EA.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water insoluble coating is made of a waterinsoluble EA.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said coating is such that, when said microcapsuleis placed in an alimentary, cosmetically or pharmaceutically acceptablemedium:

said OA is not degraded by element(s) of said medium, and

said element(s) of the medium is (are) not degraded by said OA.

By “OA not degraded by element(s)”, it means that the OA is not oxidizedor modified by oxidation, in presence of element(s) of said medium.

Said degradation can be measured by standard analytical method such asHPLC, for example HPLC ascorbic acid dosage when said OA is vitamin C.

By “element(s) of the medium is (are) not degraded by said OA”, it meansthat the element(s) is (are) not directly degraded by said OA, ordegraded by product(s) issued from oxidative reactions involving saidOA.

The degradation of a given medium is measured according to criteriaknown by those skilled in the art.

For example, when said OA is ascorbic acid, a medium containing ironsalts preferably under Fe²⁺ salt, would lead to the formation in themedium of iron ascorbate detectable with its specific black color.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said coating is such that, when said microcapsuleis placed in a fermented food composition, in particular in a fermentedvegetal milk composition:

said OA is not degraded by element(s) of said composition, and

said element(s) of the composition is (are) not degraded by said OA,

provided said composition is not a fermented dairy food composition.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said coating is such that, when said microcapsuleis placed in an unfermented food composition, in particular in anunfermented dairy or an unfermented vegetal milk composition:

said OA is not degraded by element(s) of said composition, and

said element(s) of the composition is (are) not degraded by said OA.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said coating is such that, when said microcapsuleis placed in a alimentary, cosmetically or pharmaceutically acceptablemedium comprising globular proteins, in particular a medium comprisingor consisting in an unfermented dairy or an unfermented vegetal milkcomposition and a medium comprising or consisting in a fermented vegetalmilk compositions:

said OA is not degraded by element(s) of said medium, and

said element(s) of the medium is (are) not degraded by said OA,

provided said medium do not consist in or comprise a fermented dairyfood composition.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said coating is such that, when said microcapsuleis placed in a alimentary, cosmetically or pharmaceutically acceptablemedium comprising Ca²⁺ cations, in particular a medium comprising orconsisting in an unfermented dairy or an unfermented vegetal milkcomposition and a medium comprising or consisting in a fermented vegetalmilk compositions:

said OA is not degraded by element(s) of said medium, and

said element(s) of the medium is (are) not degraded by said OA,

provided said medium do not consist in or comprise a fermented dairyfood composition.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein the mass of said coating is within the range from 3to 50%, preferably from 4 to 12%, more preferably from 5 to 8%, of thetotal mass of said microcapsule.

In an advantageous embodiment, the present invent on relates to amicrocapsule wherein said microcapsule size is in range from 1 μm to 3mm, preferably from 20 to 500 μm, more preferably from 50 to 200 μm.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is in a crystalline state.

By “crystalline state” is meant a state wherein OA molecules arearranged in an orderly, repeating pattern.

Examples of OA in a crystalline state are commercially availablecrystallized vitamins, such as crystallized vitamin C.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said core consists in or comprises an OA in acrystalline state and at least one additional element selected amongdrying agents, antioxidant agents, filmogen agents and emulsifyingagents.

Drying agents are for example starch, maltodextrin, proteins inparticular caseinates, gelatin, vegetable proteins in particular soya,wheat and pea proteins, gums in particular acacia gum as well known bythose skilled in the art.

Examples of antioxidant agents are sodium ascorbate, ascorbyl palmitate,vitamin E, and tocopherol acetate.

Filmogen agents are for example proteins in particular caseinate, gums,cellulose derivatives as well known by those skilled in the art.

Examples of emulsifying agents are lecithin, proteins, hydrolyzedproteins, modified starch as well known by those skilled in the art.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is in an amorphous state.

By “amorphous state” is meant a state wherein OA molecules are notarranged in an orderly, repeating pattern.

Compounds in an amorphous state are for instance described in Hancock etal. Journal of Pharmaceutical Sciences 1997, 86(1), pages 1-12.

Examples of OA in an amorphous state are OA amorphous solids obtained byspray-drying, under condition known by those skilled in the art: spraydrying is known to produce predominately amorphous material from ahomogenous solution, due to the almost instantaneous transition betweenliquid and solid phases.

It is noted that a microcapsule of the invention, wherein said OA isoptionally in a crystalline or an amorphous state, can let smallmolecules such as protons and water pass through its coating when saidmicrocapsule is placed in water or in an aqueous medium.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is water soluble.

When water from an external medium consisting in water or an aqueousmedium passes through said coating in an amount enough to dissolve saidwater soluble OA, a microcapsule consisting in or containing a aqueoussolution of said OA and said water insoluble coating is obtained. Such amicrocapsule allows a better bioavailability compared to particles wheresaid OA is in a solid form, as said water soluble OA is alreadydissolved in water.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said core consists in or comprises an OA in anamorphous state and at least one additional element selected amongdrying agents, antioxidant agents, filmogen agents and emulsifyingagents.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said core consists in or comprises an OA and water,the core being a solution, a liquid suspension or an emulsion of said OAin water.

In an advantageous embodiment, the present invention relates to amicrocapsule consisting in or containing:

-   -   a core consisting in or comprising an OA, water and at least one        additional element selected among drying agents, antioxidant        agents, filmogen agents and emulsifying agents, the core being a        solution, a liquid suspension or an emulsion of said OA and said        at least one additional elements in water, and    -   an insoluble coating of a EA, said coating surrounding said        core.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water soluble EA is selected from alginates ofmonovalent cations, in particular Na⁺ alginates and K⁺ alginates.

Alginates enable said OA not to be released in some external media butto be released from said microcapsules only into a specific medium, suchas in the gastrointestinal tract, wherein release of said OA is desired,in a controlled manner.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said means for inducing water insolubility are asalt wherein the cation is a divalent metallic cation, in particularCa²⁺ or Mg²⁺, said salt being in particular CaCl₂ or MgCl₂.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water insoluble coating is selected fromalginates of divalent cations, in particular Ca² alginates and Mg²alginates.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is water soluble and selected fromalginates of monovalent cations, in particular Na^(l) alginates andK^(l) alginates, and wherein said means for inducing water insolubilityare a salt wherein the cation is a divalent metallic cation, inparticular Ca²⁺ or Mg²⁺, said salt being in particular CaCl₂ or MgCl₂.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein no divalent ion, in particular no Ca²⁺, is presentin said core.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is a resin, the water solubility of whichis pH-dependent, in particular Lac gum.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is a resin that is water soluble in basicconditions and water insoluble in acidic conditions, in particularshellac gum,

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is a resin that is soluble in an organicsolvent, in particular in ethanol,

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said means for inducing water insolubility are anacid, in particular an ascorbic acid.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is water insoluble and selected fromcellulose polymers, in particular ethylcellulose.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said EA is a cellulose polymer that is soluble inan organic solvent, in particular in ethanol.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water soluble EA is lac gum, said means forinducing water insolubility consisting in particular in the drying ofsaid lac gum.

By “lac gum” is meant a purified product of the natural resinoussecretion of the insect Kerria Lacca, which is in particular found inIndia and Thailand.

By “drying of said lac gum” is meant applying a temperature that is highenough to evaporate the solvent used for the dissolution of the Lac gum,for example from about 30° C. to about 70° C. when the solvent isaqueous, or from about 10° C. to about 40° C. when the solvent is anorganic solvent, in particular ethanol.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said water soluble or organic solvent, inparticular ethanol, soluble EA is lac gum, and said means for inducingwater insolubility are an acid, in particular ascorbic acid, citricacid, acetic acid or hydrochloric acid.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is selected from the group comprisingvitamin C, vitamin B5, vitamin B6, vitamin B8, vitamin B9, vitamin A,vitamin D3, vitamin K and vitamin E.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is vitamin C, in particular natural vitaminC, synthetic vitamin C, or salts of L-ascorbic acid, more particularlysodium L-ascorbate, calcium L-ascorbate and iron L-ascorbate.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA comprises vitamin C, said OA being inparticular a fruit juice comprising vitamin C, in particular orangejuice, kiwi juice, cranberry juice or acerola juice, said fruit juicebeing optionally concentrated or dried.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA comprises vitamin C, said OA being inparticular a fruit juice comprising vitamin C, in particular orangejuice, kiwi juice, cranberry juice, acerola juice or goji juice, saidfruit juice being optionally concentrated or dried.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is vitamin C or comprises vitamin C andwherein said EA is water soluble and selected from alginates ofmonovalent cations, in particular Na⁺ alginates and K⁺ alginates.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is vitamin C or comprised vitamin C,wherein said EA is water soluble and selected from alginates ofmonovalent cations, in particular Na⁺ alginates and K⁺ alginates, andwherein said means for inducing water insolubility are a salt whereinthe cation is a divalent metallic cation, in particular Ca²⁺ or Mg²⁺,said salt being in particular CaCl₂ or MgCl₂.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is selected from the group comprisingdihydroxyacetone (DHA), enriched in omega 3 or omega 6 oil, andoxidizable enzymes, in particular superoxydismutase (SOD).

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is superoxydismutase (SOD), in particularfreeze-dried SOD or spray-dried SOD.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is SOD, said EA is water soluble or organicsolvent, in particular ethanol, soluble, said water soluble or organicsolvent-soluble EA being lac gum, and said means for inducing waterinsolubility consist in the drying of said lac gum.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is SOD, said water soluble or organicsolvent, in particular ethanol, soluble EA is lac gum, and said meansfor inducing water insolubility are an acid, in particular ascorbicacid, citric acid, acetic acid or hydrochloric acid.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is SOD, said EA is water soluble, saidwater soluble EA being selected from alginates of monovalent cations, inparticular Na⁺ alginates and K⁺ alginates, and said means for inducingwater insolubility are a salt wherein the cation is a divalent metalliccation, in particular Ca²⁺ or Mg²⁺, said salt being in particular CaCl₂or MgCl₂.

In an advantageous embodiment, the present invention relates to amicrocapsule wherein said OA is SOD and said EA is water insoluble.

In another aspect, the present invention relates to a process ofpreparation of microcapsules described above, comprising the followingsteps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally said EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;

to obtain particles consisting in said OA, or particles comprising saidOA, and said EA and/or at least one additional element,

-   spraying on said particles an insoluble EA or means for inducing    water insolubility of EA comprised in said particle, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core consisting in said OA, or comprising said    OA, and said EA and/or at least one additional element.

It is noted that said OA is, in said obtained microcapsule,predominantly in an amorphous state as spray drying is known to producepredominantly amorphous material from a homogenous solution, due to thealmost instantaneous transition between liquid and solid phases

The obtained microcapsules comprising said OA predominantly in anamorphous state have typically a size comprised from 1 μm to 1000 μm,preferably from 20 μm to 500 μm, and more preferably from 50 to 200 μm.

The present invention also relates to a process of preparation ofmicrocapsules comprising the following steps:

-   a spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally said EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles consisting in said OA, or particles        comprising said OA, and said EA and/or at least one additional        element, the outer part of said particles being in a solid form,-   spraying on said particles an insoluble EA or means for inducing    water insolubility of EA comprised in said particle, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core consisting in said OA, or comprising said    OA, and said EA and/or at least one additional element,-   with the proviso that:

said core does not consist in or comprise a metal oxide, and

said coating does not comprise a disintegrant, in particular sodiumstarch glycolate.

In an advantageous embodiment, the present invention relates to aprocess of preparation of microcapsules described above, comprising thefollowing steps:

-   a spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally said EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles consisting in said OA in an amorphous state,        or particles comprising said OA in an amorphous state, and said        EA and/or at least one additional element,-   spraying on said particles an insoluble EA or means for inducing    water insolubility of EA comprised in said particle, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core consisting in said OA in an amorphous    state, or comprising said OA in an amorphous state, and said EA    and/or at least one additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising, after said spray-drying and spraying steps, a stepof drying said microcapsules to obtain dried microcapsules.

In an advantageous embodiment, the present invention relates to aprocess wherein said spray-drying step is done in a spray-dryer and saidspraying step and drying step are done in a coating device by spray, inparticular a coating device by spray comprising a fluidized bed.

Examples of spray-dryer wherein the spray-drying step can be performedare single effect spray-drying towers, toll form spray-drying towers,belt dryer and multiple effect spray-drying towers with internal orexternal fluid bed.

Examples of coating device by spray wherein the spraying step can beperformed are fluidized beds, top spray, tangential spray, bottom sprayor wurster devices, batch process devices or continuous devices ashorizontal fluid bed or multicellular fluid bed; these devices being asdescribed in Vandamme et al Mieroencapsulation; Tec & Doc; 2007; Chapter10.

In an advantageous embodiment, the present invention relates to aprocess wherein said spray-drying step, spraying step and drying stepare done in the same spray-dryer.

Interestingly, the Inventors have found that the microcapsules, obtainedby a process wherein said spray-drying step, spraying step and dryingstep are done in the same spray-dryer, surprisingly protect said OA fromoxidation by a given alimentary, cosmetically or pharmaceuticallyacceptable medium in which said microcapsules are placed, and saidmedium from said OA.

Examples of spray-dryer wherein the spray-drying step and the sprayingstep can be performed are single effect spray-drying towers, toll formspray-drying towers, belt dryer and multiple effect spray-drying towerswith internal or external fluid bed.

In an advantageous embodiment, the present invention relates to aprocess of preparation of microcapsules described above, comprising thefollowing steps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally said EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles consisting in said OA in an amorphous state,        or particles comprising said OA in an amorphous state, and said        EA and/or at least one additional element,

spraying on said particles an insoluble EA or means for inducina waterinsolubility of EA comprised in said particle, to obtain microcapsuleswith a water insoluble coating, said water insoluble coating surroundinga core consisting in said OA in an amorphous state, or comprising saidOA in an amorphous state, and said EA and/or at least one additionalelement,

drying said microcapsules to obtain dried microcapsules, saidspray-drying step, spraying step and drying step being done in the samespray-dryer.

In an advantageous embodiment, the present invention relates to aprocess wherein said means for inducing water insolubility are an agentchemically reacting with said EA.

In an advantageous embodiment, the present invention relates to aprocess wherein said means for inducing water insolubility are an acid,abuse or a buffer.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

a spray-drying a liquid mixture consisting in or comprising:

-   -   said OA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles consisting in said OA, or particles        comprising said OA and said at least one additional element,

-   spraying on said particles a water insoluble EA, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core consisting in said OA, or comprising said    OA and said at least one additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   a water soluble EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles comprising said OA, said EA and optionally        said at least one additional element,-   spraying on said particles means for inducing water insolubility of    EA comprised in said is particle, to obtain microcapsules with a    water insoluble coating, said water insoluble coating surrounding a    core comprising said OA, said EA and optionally at least one    additional element.

Interestingly, the Inventors have found that the fact of inducing waterinsolubility of EA by spraying said means, in particular in aqueoussolution, on solid dried particles (comprising said OA and said EA)obtained by spray-drying, surprisingly forms a protective coating thathas the ability to protect said OA from oxidation by a given alimentary,cosmetically or pharmaceutically acceptable medium in which saidmicrocapsules are placed, and said medium from said OA.

Said process of the invention, wherein water insolubility of EA isinduced by spraying means on solid dried particles is a spray-dryingprocess with respect to said particles, which are dried before saidspraying.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles comprising said OA, said alginate and        optionally said at least one additional element,-   a spraying on said particles means for inducing water insolubility    of alginate comprised in said particle, to obtain microcapsules with    a water insoluble coating, said water insoluble coating surrounding    a core comprising said OA, said EA and optionally at least one    additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   a spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain particles comprising said OA, said alginate and        optionally said at least one additional element,-   spraying on said particles an aqueous solution of a salt wherein the    cation is a divalent metallic cation, in particular Ca²⁺ or Mg²⁺,    said salt being in particular CaCl₂ or MgCl₂, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core comprising said OA, said EA and    optionally at least one additional element;-   a drying said microcapsules to obtain dried microcapsules.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a homogenous aqueous solution.

The liquid mixture is a homogenous aqueous solution when said OA, saidEA and, provided an additional element is present in said mixture, saidadditional element are water soluble.

When the liquid mixture is a homogenous aqueous solution, the size ofthe obtained microcapsules are driven by the parameters of spray-drying,and not by the characteristics of said water soluble OA.

The microcapsules obtained have typically a size comprised from 1 μm to1000 μm, preferably from 20 μm to 500 μm, and more preferably from 50 to200 μm.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a solid-in-liquid suspension oran emulsion.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a homogenous aqueous solutionconsisting in or comprising said OA.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a homogenous aqueous solutionconsisting in or comprising said OA and at least one additional elementselected among drying agents, antioxidant agents, filmogen agents andemulsifying agents.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a homogenous aqueous solutionconsisting in or comprising said OA and said water soluble EA.

In an advantageous embodiment, the present invention relates to aprocess wherein said liquid mixture is a homogenous aqueous solutionconsisting in or comprising said OA, said water soluble EA, and at leastone additional element selected among drying agents, antioxidant agents,filmogen agents and emulsifying agents.

In another aspect, the present invention relates to a process comprisinga step of spraying on particles consisting in said OA, or particlescomprising said OA, and said EA and/or at least one additional elementselected among drying agents, antioxidant agents, filmogen agents andemulsifying agents, an insoluble EA or means for inducing waterinsolubility of EA comprised in said particle, to obtain microcapsuleswith a water insoluble coating, said water insoluble coating surroundinga core consisting in said OA, or comprising said OA, and said EA and/orat least one additional element.

In an advantageous embodiment, the present invention relates to aprocess comprisina, after said spraying step, a step of drying saidmicrocapsules to obtain dried microcapsules.

In an advantageous embodiment, the present invention relates to aprocess wherein said means for inducing water insolubility are an agentchemically reacting with said EA,

In an advantageous embodiment, the present invention relates to aprocess wherein said means for inducing water insolubility are an acid,abuse, or a buffer.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles consisting in saidOA, or particles comprising said OA and at least one additional elementselected among drying agents, antioxidant agents, filmogen agents andemulsifying agents, a water insoluble coating to obtain microcapsuleswith a water insoluble coating, said water insoluble coating surroundinga core consisting in said OA, or comprising said OA, and said at leastone additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying in a device on particlescomprising:

-   -   said OA,    -   a water soluble EA, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmoaen agents and emulsifying        agents,        means for inducing water insolubility of EA comprised in said        particle, to obtain microcapsules with a water insoluble        coating, said water insoluble coating surrounding a core        comprising said OA, and said EA and/or at least one additional        element.

Interestingly, the Inventors have found that the fact of inducina waterinsolubility of EA by spraying said means, in particular in aqueoussolution, on solid dried particles (comprising said OA and said EA), forexample obtained by spray-drying, surprisingly forms a protectivecoating that has the ability to protect said OA from oxidation by agiven alimentary, cosmetically or pharmaceutically acceptable medium inwhich said microcapsules are placed, and said medium from said OA.

Examples of device wherein the spraying step can be performed arefluidized beds, top spray, tangential spray, bottom spray or wursterdevices, batch process devices or continuous devices as horizontal fluidbed or multicellular fluid bed; these devices being as described inVandamme et al Microeneapsulation; Tec & Doc; 2007; Chapter 10.

Said process of the invention, wherein water insolubility of EA isinduced by spraying means on solid dried particles is a spray-dryingprocess with respect to said particles, which are dried before saidspraying.

Two cases can be distinguished:

-   -   the first one occurs when means for inducina water insolubility        involves all the EA comprised in said particles; in this case,        microcapsules with a core consisting in said OA, or comprising        said OA, and optionally at least one additional element, are        obtained;    -   the second one occurs when means for inducing water insolubility        involves only a part of the EA comprised in said particles, in        particular EA present on or near the surface of said particles;        in that case, microcapsules with a core comprising said OA, said        EA and optionally at least one additional element, are obtained.

The nature of the means for inducing water insolubility, the mass of EAin respect of the total mass of said microcapsule, and the distributionof EA in said particles are factors that can lead to the first or thesecond case.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles comprising:

-   -   said OA,    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmoaen agents and emulsifying        agents,        means for inducing water insolubility of alginate comprised in        said particle, to obtain microcapsules with a water insoluble        coating, said water insoluble coating surrounding a core        comprising said OA, and said alginate and/or at least one        additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles comprising:

-   -   said OA,    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents,        an aqueous solution of a salt wherein the cation is a divalent        metallic cation, in particular Ca²⁺ or M²⁺, said salt being in        particular CaCl₂ or MgCl₂, to obtain microcapsules with a water        insoluble coating, said water insoluble coating surrounding a        core comprising said OA, and said alginate and/or at least one        additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles comprising:

-   -   said GA,    -   lac gum, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents,        means for inducing water insolubility of lac gum comprised in        said particle, to obtain microcapsules with a water insoluble        coating, said water insoluble coating surrounding a core        comprising said OA and/or at least one additional element.

Said particles comprising:

-   -   said OA,    -   lac gum, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, fihnogen agents and emulsifying        agents,        are for example obtained by spraying lac gum, said lac gum being        in particular dissolved in water or ethanol, on particles        consisting in said OA or comprising said OA and at least one        additional element selected among drying agents, antioxidant        agents, filmogen agents and emulsifying agents.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles comprising:

-   -   said GA,    -   lac gum, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents,        an aqueous solution of an acid, in particular ascorbic acid,        citric acid, acetic acid or hydrochloric acid, to obtain        microcapsules with a water insoluble coating, said water        insoluble coating surrounding a core comprising said OA and/or        at least one additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of spraying on particles comprising:

-   -   said OA,    -   lac gum, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents,        an aqueous solution of an acid, in particular ascorbic acid,        citric acid, acetic acid or hydrochloric acid, to obtain        microcapsules with a water insoluble coating, said water        insoluble coating surrounding a core comprising said OA and/or        at least one additional element,        said OA being superoxydismutase (SOD), in particular        freeze-dried SOD or spray-dried SOD.

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by coating said OA in asolid state with said water soluble EA and optionally at least oneadditional element selected among drying agents, antioxidant agents,filmogen agents and emulsifying agents.

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by coating said OA in acrystalline state with said water soluble EA and optionally at least oneadditional element selected among drying agents, antioxidant agents,filmogen agents and emulsifying agents.

Thus, the microcapsules obtained after spraying on said particles meansfor inducing water insolubility of said EA comprise a core consisting inor comprising OA in a crystalline state.

It is noted that the size of microcapsules is driven by the size of OAparticles in crystalline state.

For example, the size of microcapsules obtained from vitamin C particleshaving a size comprised from 20 to 200 μm is comprised from 20 to 350μm.

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by co-spraying a homogenousaqueous solution comprising:

-   -   said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, fihnogen agents and emulsifying        agents;        and said OA in a solid state.

By co-spraying is meant that said homogenous aqueous solution and saidOA in a solid state are sprayed jointly in such a manner that thesprayed homogenous aqueous solution films the particles of OA in a solidstate to give particles that are totally filmed by the EA.

In an advantageous embodiment, co-spraying is performed with twoseparate means of pulverization, in particular two separate nozzles.

In an advantageous embodiment, co-spraying is performed with twocombined means of pulverization, in particular a trifluid nozzle.

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by co-spraying a homogenousaqueous solution comprising:

-   -   said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmoaen agents and emulsifying        agents;        and said OA in a crystalline state.

Thus, the microcapsules obtained after spraying on said particles meansfor inducing water insolubility of said EA comprise a core consisting inor comprising OA in a crystalline state.

It is noted that the size of microcapsules is driven by the size of OAparticles in crystalline state.

For example, the size of microcapsules obtained from vitamin C particleshaving a size comprised from 20 to 200 μm is comprised from 20 to 350μm.,

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by co-spraying a homogenousaqueous solution comprising said water soluble EA and said OA in a solidstate.

In an advantageous embodiment, the present invention relates to aprocess wherein said particles are obtained by co-spraying in aspray-dryer a homogenous aqueous solution comprising:

-   -   said water soluble EA;    -   at least one additional element selected among drying agents,        antioxidant agents, filmogen agents and emulsifying agents;        and said OA in a solid state.

In an advantageous embodiment, the present invention relates to aprocess wherein particles are obtained in a spray-dryer.

In an advantageous embodiment, the present invention relates to aprocess wherein said spraying of said means for inducing waterinsolubility of EA is performed in the spray-dryer used to obtain saidparticles.

Examples of spray-dryer wherein the spray-drying step and the sprayingstep can be performed are single effect spray-drying towers, toll formspray-drying towers, belt dryer and multiple effect spray-drying towerswith internal or external fluid bed.

Interestingly, the Inventors have found that the microcapsules, obtainedby a process wherein said spraying of said agent is performed in thesame spray-dryer as the one used to obtain said particles, in a singlestep of obtaining particles by spray-drying and spraying them with saidagent, surprisingly protect said OA from oxidation by a givenalimentary, cosmetically or pharmaceutically acceptable medium in whichsaid microcapsules are placed, and said medium from said OA.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   a co-spraying in a spray-dryer a homogenous aqueous solution    comprising:    -   a said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        and said OA in a crystalline state, to obtain particles        comprising:    -   said OA in a crystalline state,    -   said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, fihnogen agents and emulsifying        agents,-   spraying in a device on said particles means for inducing water    insolubility of EA comprised in said particles, to obtain    microcapsules with a water insoluble coating, said water insoluble    coating surrounding a core comprising said OA in a crystalline    state, and said EA and/or at least one additional element.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   co-spraying in a spray-dryer a homogenous aqueous solution    comprising:    -   said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, fihnogen agents and emulsifying        agents;        and said OA in a crystalline state, to obtain particles        comprising:    -   said OA in a crystalline state,    -   said water soluble EA,    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents,-   spraying in the same spray-dryer on said particles means for    inducing water insolubility of EA comprised in said particles, to    obtain microcapsules with a water insoluble coating, said water    insoluble coating surrounding a core comprising said OA in a    crystalline state, and said EA and/or at least one additional    element.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   co-spraying in a spray-dryer a homoaenous aqueous solution    comprising:    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        and said OA in a solid state, to obtain particles comprising:    -   said OA,    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and optionally at least one additional element        selected among drying agents, antioxidant agents, filmogen        agents and emulsifying agents,-   a spraying in a device on said particles an aqueous solution of a    salt wherein the cation is a divalent metallic cation, in particular    Ca²⁺ or Mg²¹⁻, said salt being in particular CaCl₂ or MgCl₂, to    obtain microcapsules with a water insoluble coating, said water    insoluble coating surrounding a core comprising said OA, and said    alginate and/or at least one additional element,-   drying said microcapsules to obtain dried microcapsules.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   co-spraying in a spray-dryer a homogenous aqueous solution    comprising:    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        and said OA in a solid state, to obtain particles comprising:    -   said GA,    -   alginate of monovalent cation, in particular Na⁺ alginate and K⁺        alginate, and optionally at least one additional element        selected among drying agents, antioxidant agents, filmogen        agents and emulsifying agents,-   spraying in the same spray-dryer on said particles an aqueous    solution of a salt wherein the cation is a divalent metallic cation,    in particular C²⁺ or Mg²⁺, said salt being in particular CaCl₂ or    MgCl₂, to obtain microcapsules with a water insoluble coating, said    water insoluble coating surrounding a core comprising said OA, and    said alginate and/or at least one additional element,-   a drying said microcapsules to obtain dried microcapsules.

In an advantageous embodiment, the present invention relates to aprocess comprising a step of co-spraying in a spray-dryer:

-   a a liquid mixture consisting in or comprising:    -   said OA;    -   a water soluble EA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        and-   a means for inducing water insolubility of said EA,    to obtain microcapsules with a water insoluble coating, said water    insoluble coating surrounding a core comprising said OA, said EA and    optionally at least one additional element.

By co-spraying is meant that said liquid mixture and said means forinducing water insolubility of said EA are sprayed jointly in such amanner that the sprayed means for inducing water insolubility filmparticles of OA and optionally at least one additional element.

In an advantageous embodiment, co-spraying is performed with twoseparate means of pulverization, in particular two separate nozzles.

In an advantageous embodiment, co-spraying is performed with twocombined means of pulverization, in particular a trifluid nozzle.

In another aspect, the present invention relates to a process comprisingthe following steps:

-   a spraying, on particles consisting in said OA, or particles    comprising said OA and at least one additional element selected    among drying agents, antioxidant agents, filmogen agents and    emulsifying agents, a water soluble EA to obtain particles    surrounded by said EA;-   drying said particles surrounded by said EA, to obtain microcapsules    with a water insoluble coating, said water insoluble coating    surrounding a core comprising said OA, and optionally at least one    additional element,    said water soluble EA being in particular lac gum, said lac gum    being in particular dissolved in water or ethanol.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   spraying, on particles consisting in said OA, or particles    comprising said OA and at least one additional element selected    among drying agents, antioxidant agents, filmogen agents and    emulsifying agents, a water soluble or organic solvent, in    particular ethanol, soluble EA to obtain particles surrounded by    said EA;-   drying said particles surrounded by said EA, to obtain microcapsules    with a water insoluble coating, said water insoluble coating    surrounding a core comprising said OA, and optionally at least one    additional element,    said OA being superoxydismutase (SOD), in particular freeze-dried    SOD or spray-dried SOD, said water soluble or organic    solvent-soluble EA being in particular lac gum, said lac gum being    in particular dissolved in water or ethanol.

In an advantageous embodiment, the present invention relates to aprocess wherein said spraying step and drying step are done in aspray-dryer.

In an advantageous embodiment, the present invention relates to aprocess wherein said spraying step and drying step are done in a coatingdevice by spray, in particular a coating device by spray comprising afluidized bed.

Examples of device wherein the spraying step can be performed arefluidized beds, top spray, tangential spray, bottom spray or wursterdevices, batch process devices or continuous devices as horizontal fluidbed or multicellular fluid bed; these devices being as described inVandamme et al Microencapsulation; Tee & Doc; 2007; Chapter 10.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain spray-dried particles consisting in said OA, or        particles comprising said OA and at least one additional        element,-   a spraying on said particles a water soluble or organic solvent, in    particular ethanol, soluble EA, to obtain particles surrounded by    said EA;-   drying said particles surrounded by said EA, to obtain microcapsules    with a water insoluble coating, said water insoluble coating    surrounding a core comprising said OA, and optionally at least one    additional element,    said water soluble or organic solvent-soluble EA being in particular    km gum, said lac gum being in particular dissolved in water or    ethanol.

In an advantageous embodiment, the present invention relates to aprocess comprising the following steps:

-   spray-drying a liquid mixture consisting in or comprising:    -   said OA;    -   optionally at least one additional element selected among drying        agents, antioxidant agents, filmogen agents and emulsifying        agents;        to obtain spray-dried particles consisting in said OA, or        particles comprising said OA and at least one additional        element,-   a spraying on said particles a water soluble or organic solvent, in    particular ethanol, soluble EA, to obtain particles surrounded by    said EA;-   drying said particles surrounded by said EA, to obtain microcapsules    with a water insoluble coating, said water insoluble coating    surrounding a core comprising said OA, and optionally at least one    additional element,    said OA being superoxydismutase (SOD), in particular freeze-dried    SOD or spray-dried SOD, said water soluble or organic    solvent-soluble EA being in particular lac gum, said lac gum being    in particular dissolved in water or ethanol.

In an advantageous embodiment, the present invention relates to aprocess wherein said spray-drying step, spraying step and drying stepare done in a spray-dryer.

In an advantageous embodiment, the present invention relates to aprocess wherein said spray-drying step is done in a spray-dryer and saidspraying step and drying step are done in a coating device by spray, inparticular a coating device by spray comprising a fluidized bed.

Examples of spray-dryer wherein the spray-drying step can be performedare single effect spray-drying towers, toll form spray-drying towers,belt dryer and multiple effect spray-drying towers with internal orexternal fluid bed.

Examples of device wherein the spraying step can be performed arefluidized beds, top spray, tangential spray, bottom spray or wursterdevices, batch process devices or continuous devices as horizontal fluidbed or multicellular fluid bed; these devices being as described inVandamme et al Microencapsulation; Tec & Doc; 2007; Chapter 10.

In another aspect, the present invention relates to a food compositioncomprising microcapsules described above, provided said food compositionis not a fermented dairy food composition.

In another aspect, the present invention relates to a beveragecomposition comprising microcapsules described above, provided saidbeverage composition is not a fermented dairy food composition.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising microcapsules described above, provided said foodcomposition is not a fermented dairy food composition and said foodcomposition does not comprise vitamin C or a chemical derivative ofvitamin C.

In an advantageous embodiment, the present invention relates to abeverage composition comprising microcapsules described above, providedsaid beverage composition is not a fermented dairy food composition andsaid beverage composition does not comprise vitamin C or a chemicalderivative of vitamin C.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising unfermented dairy products.

In an advantageous embodiment, the present invention relates to abeverage composition comprising unfermented dairy products, inparticular milk.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising a vegetal milk, in particular almond, coconut,rice and soy milk, said composition being unfermented or fermented.

In an advantageous embodiment, the present invention relates to abeverage composition comprising a vegetal milk, in particular almond,coconut, rice and soy milk, said composition being unfermented orfermented.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising one or more fruits in addition of saidmicrocapsules.

In an advantageous embodiment, the present invention relates to abeverage composition comprising one or more fruits in addition of saidmicrocapsules.

In an advantageous embodiment, the present invention relates to a foodcomposition wherein said food composition is a fruit juice composition.

In an advantageous embodiment, the present invention relates to abeverage composition wherein said beverage composition is a fruit juicecomposition.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising one or more vegetables in addition of saidmicrocapsules.

In an advantageous embodiment, the present invention relates to abeverage composition comprising one or more vegetables in addition ofsaid microcapsules.

In an advantageous embodiment, the present invention relates to a foodcomposition comprising:

-   -   said microcapsules,    -   water,    -   one or more sugar and/or sweetener    -   flavoring(s).

In an advantageous embodiment, the present invention relates to abeverage composition comprising:

-   -   said microcapsules,    -   water,    -   one or more sugar and/or sweetener    -   flavoring(s).

In an advantageous embodiment, the present invention relates to abeverage composition comprising:

-   -   said microcapsules, wherein said OA is in particular SOD,    -   water,    -   optionally a fruit juice,    -   optionally at least one vitamin, in particular vitamin C or        riboflavin,    -   optionally proteins.

In an advantageous embodiment, the present invention relates to apulverulent composition for the preparation of an instant drinkcomprising:

-   -   said microcapsules, wherein said OA is in particular SOD,    -   optionally at least one vitamin, in particular vitamin C or        riboflavin,    -   optionally proteins,        said pulverulent composition to be mixed with water and/or at        least a fruit juice before use.

In another aspect, the present invention relates to a cosmeticcomposition comprising microcapsules described above.

In another aspect, the present invention relates to a pharmaceuticalcomposition comprising microcapsules described above.

In another aspect, the present invention relates to the use ofmicrocapsules described above for the preparation of a food composition.

In another aspect, the present invention relates to the use ofmicrocapsules described above for the preparation of a cosmeticcomposition.

In another aspect, the present invention relates to the use ofmicrocapsules described above for the preparation of a pharmaceuticalcomposition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 presents a process wherein vitamin C particles in a crystallineform (1) are coated in a fluid bed (2) with an aqueous alginate solution(3) sprayed on said particles. Obtained particles (7) are then placed(5) in the same or another fluid bed (2bis). Alginate solution or acidor base or buffer or salt solution (4) is then sprayed on the particles(7) or the said particles are solely dried. Microcapsules (8) arerecovered (6).

FIG. 2 presents a process wherein, alginate and optionally additionelements are solubilized in water, with solubilized or fruit juicevitamin C: solution (Ibis), or with crystalline vitamine C: suspension(1Bis) and then sprayed in the spray-dryer (9). Either the obtainedparticles (7) are then transferred (10) in a fluid bed (2bis) and analginate solution or acid or base or buffer or salt solution (4) issprayed on said particles (7), or an alginate solution or acid or baseor buffer solution (4) is in parallel sprayed in the same said spraydryer (9), and then optionally dried. Microcapsules (8) are recovered(6).

FIGS. 3, 4 and 5 present scanning electron microscope (SEM) analyses ofmicrocapsules obtained by the process respectively described in example4, 2 and 3.

FIG. 6 present scanning electron microscope (SEM) analysis of amicrocapsule obtained by the process described in example 1, which wasfractured prior to said analysis.

Said SEM analyses were performed with a Quanta200, ESEM FEG typemicroscope (Scanning Electron Microscopes, Field emission gun), at awater vapor pressure of 1.2 mbar, a voltage of 20 kV and a currentdensity of 4 (on a scale ranging from 0 to 7),

FIG. 7A presents the vitamin C monitoring on a microcapsule obtained bythe process described in example 4.

Said microcapsules were packed in heat-sealed aluminum bags, stored at4° C. or 20° C. and monitored over time, over a period of 3 months. Theresults show that there is no degradation of vitamine C content after 3months of storage. Vitamin C monitoring was performed according tostandard NF 14130 (by HPLC).

FIG. 7B presents the vitamin C monitoring on a microcapsule obtained bythe process described in example 4.

Said microcapsules were packed in heat-sealed aluminum bags, stored at4° C. or 20° C. and monitored over time, over a period of 6 months. Theresults show that there is no degradation of vitamine C content after 6months of storage, Vitamin C monitoring was performed according tostandard NF 14130 (by HPLC).

FIG. 8 presents the following of the size of microcapsule obtained bythe process described in example 4 over time, when said microcapsulesare placed in water at room temperature. Size is expressed in D(v; 0.5)in microns and is measured using a laser particle sizer MalvernInstrument, MSS Type, model MasterSizer, Dv(0.5) being the mean particlesize of the obtained microcapsule size distribution.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is further illustrated by the following examples.

EXAMPLES Example 1 Microcapsules Containing Vitamin C

3.3 kg of crystalline vitamin C were fluidized in a fluid bed (WSG5GLATT), inlet air temperature is 60° C.

2.9 kg of a 5% solution of sodium alginate in dry matter, containing 10g of ascorbyl palmitate were sprayed on the fluidized particles with abifluid nozzle (spraying system SS 2050), on a top-spray position, aswell known by those skilled in the art (in particular Vandamme et alMicroencapsulation; Tee &. Doc; 2007), and then dried. Solid particlesare obtained.

Another 1.1 Kg of a 5% solution of sodium alginate in dry matter wasthen spray dried on the fluidized particles. A final drying step of 30mn was then processed at a maximum temperature of 50° C. on themicrocapsules.

The final microcapsules had a moisture content of 1.1% (infraredmeasurement). Particle size distribution was below 300 μm (mean particlesize measured by light diffraction on Malvern sizer) and bulk densitywas of 850 g/l.

Example 2 Microcapsules Containing Vitamin C

A solution was prepared with 7.8 kg of crystalline vitamin C in 31.2 kgof water at room temperature. 3.78 kg of modified starch, 0.5 kg ofcarboxymethylcellulose and 0.8 kg of alginate were added to thispreparation. The preparation was then homogenized at a pressure of 200bars. The homogenized preparation was then dried in a single stage dryer(Minor production tower, GEA-NIRO) with a rotary atomizer, with an inlettemperature of 150° C. and outlet temperature of 85° C. Solid particlesare obtained. 4.6 kg of a calcium chloride solution at 5% dry matter wasthen sprayed on the fluidized particles on a fluidized bed (WSGS, GLATT)as well known by those skilled in the art. The final microcapsules hadan average size of 210 μm (mean particle size measured by lightdiffraction on Malvern sizer), a moisture content of 2.3% and a bulkdensity of 650 g/l.

Example 3 Microcapsules Containing Vitamin C from Acerola Juice

2.6 kg of acerola fruit juice, with a vitamin C content of 20.9 g /100ml, was mixed with 0.6 kg of starch, 0.08 kg of carboxy methylcellulose, 0.10kg of alginate and 7.8 kg of water. The preparation washomogenized at 200 bars.

The homogenized preparation was then dried in a single stage dryer(Minor production tower, GEA-NIRO) with a rotary atomizer, with an inlettemperature of 125° C. and outlet temperature of 90° C. Solid particlesare obtained.

0.6 kg of a calcium chloride solution at 5% dry matter was then sprayedon the fluidized particles on a fluidized bed (WSGS, GLATT) as wellknown by those skilled in the art.

The final microcapsules had an average size of 80 μm (mean particle sizemeasured by light diffraction on Malvern sizer), a moisture content of5% and a hulk density of 630 g/l.

Example 4 Microcapsules Containing VitamnbxC

3.3 kg of crystalline vitamin C, were fluidized in a fluid bed (WSG5(GLATT), inlet air temperature is 60° C.

2.9 kg of a 5% solution of sodium alginate in dry matter, containing 10g of ascorbyl palmitate were sprayed on the fluidized particles with abifluid nozzle (spraying system SS 2050), on a top-spray position, aswell known by those skilled in the art (in particular

Vandamme et al Microencapsulation; Tec & Doc; 2007). Solid particles areobtained. 0.8 Kg of a calcium chloride solution, 5% dry matter was thenspray dried on the fluidized particles. The final microcapsules had amoisture content of 2.8% (infrared measurement). Particle sizedistribution was below 300 μM (mean particle size measured by lightdiffraction on Malvern sizer) and bulk density was of 800 g/l.

Example 5 Microcapsules Containing Vitamin C

A solution was prepared with 7.8 kg of crystalline vitamin C in 31.2 kgof water at room temperature. 3.78 kg of modified starch, 0.5 kg ofcarboxymethylcellulose and 0.8 kg of alginate were added to thispreparation. The preparation was then homogenized at a pressure of 200bars. 4.6 kg of a calcium chloride solution at 5% dry matter wasprepared. The homogenized preparation was then sprayed in a single stagedryer (Minor production tower, GEA-NIRO) with a rotary atomizer, and thecalcium chloride solution was also sprayed in the same time in thechamber of the same dryer. Drying step was made with an inlettemperature of 150° C. and outlet temperature of 75° C.

The final microcapsules had an average size of 80 μm (mean particle sizemeasured by light diffraction on Malvern sizer), a moisture content of6.0% and a bulk density of 600 g/l.

Example 6 Microcapsules Containing Omega 3 Enriched Oil

1.3 kg of omega 3 enriched oil was mixed with 3.8 kg of modified starch,0.7 kg of carboxymethylcellulose, 0.8 kg of alginate and 11.8 kg ofwater.

The preparation was homogenized at 200 bars.

The homogenized preparation was then dried in a single stage dryer(Minor production tower, GEA-NIRO) with a rotary atomizer, with an inlettemperature of 150° C. and outlet temperature of 80° C. Particles with asolid outer part are obtained.

4.1 kg of a calcium chloride solution at 5% dry matter was then sprayedon the fluidized particles on a fluidized bed (WSG5, GLATT) as wellknown by those skilled in the art.

The final microcapsules had an average size of 80 μm (mean particle sizemeasured by light diffraction on Malvern sizer), a moisture content of3.2% and a bulk density of 470 g/l.

Example 7 Microcapsules Containing Vitamin C Coated with ethylcellulose

2.47 kg of crystalline vitamin C were fluidized in a fluid bed (WSG5,GLATT). Inlet temperature did not exceed 40° C.

2.47 kg of ethylcellulose were prepared in ethanol at 10% dry matter andsprayed using a bi-fluid nozzle (spraying system SS 2050), on a topspray position on the fluidized crystalline vitamin.

After the coating, the microcapsules were dried in the fluidized bedchamber for 10 mn. The final microcapsules had a moisture content of1.1% (infrared moisture measurement, 105° C.) and a particle sizedistribution of 130 μm (mean particle size measured by light diffractionon Malvern sizer).

Example 8 Microcapsules Containing SOD

3.3 kg of freeze dried superoxydismutase enzyme (SOD) were fluidized ina fluid bed (WSG5, GLATT). Inlet temperature was 60° C.

2.9 kg of a 5% solution of sodium alginate in dry matter, containing 10g of ascorbyl palmitate were sprayed on the fluidized particles with abifluid nozzle (spraying system SS 2050), on a top-spray position, aswell known by those skilled in the art (in particular Vandamme et alMicroencapsulation; Tee & Doc; 2007). Solid particles are obtained.

0.8 Kg of a calcium chloride solution, 5% dry matter was then spraydried on the fluidized particles.

The final microcapsules had a moisture content of 1.3%. Particle sizedistribution was below 300 μm (mean particle size measured by lightdiffraction on Malvern sizer) and bulk density was of 410 g/l.

Example 9 Microcapsules Containing SOD Coated with Lac Gum

500 g of freeze-dried of superoxydismutase enzyme (SOD) were weightedand put into a fluid bed (GPCG1, GLATT) and fluidized. 516 g of Lac gum(ie: 500 g of Dry Lac gum) were dissolved at 20% dry matter and sprayedon the fluidized SOD. Process temperature of the powder did not exceed36° C. Final product had a moisture content of 2.1% and an averageparticle size mean of 370 μm (Median diameter Dv(0.5) measured by laserparticle sizer Malvern)

Analyses of SOD activity were made in water solution at pH 2.9 and 7.0.

No SOD activity was observed at pH 2.9 although more than 95% of SODactivity is recovered at pH 7.0.

Example 10 Microcapsules Containing Ferrous Ascorbate

1.2 kg of ferrous ascorbate were weighted and put into a fluid bed(GPCG1, GLATT), inlet air temperature is 80° C.

1.1 kg of a 5% solution of sodium alginate in dry matter were sprayed onthe fluidized particles with a bifluid nozzle, on a top-spray position.Solid particles are obtained. 0.3 Kg of a calcium chloride solution, 5%dry matter was then spray dried on the fluidized particles.

The final microcapsules had a moisture content of 6%. Particle sizedistribution was below 300 μm (mean particle size measured by lightdiffraction on Malvern sizer) and bulk density was of 420 g/l.

Example 11 Microcapsules Containing DHA

500 g of crystalline Dihydroxyacetone (DHA) were weighted and put into afluid bed (GPCG1, GLATT) and fluidized. 125 g of Lac gum were dissolvedat 24% dry matter and sprayed on the fluidized DHA.

The microcapsules obtained had a moisture content of 4.1%, and aparticle size distribution of 790 μm (mean diameter, measured by laserdiffraction on Malvern sizer)

Evaluation of coloration was made in water at pH 4.0 and 7.0.

No coloration occurred after 1H at pH 4.0, although in water at pH 7.0an orange coloration appeared in the first 15 mn and became brownishafter 1H showing the protective effect of the microcapsule of theinvention in low pH conditions.

Example 12 Microcapsules Containing SOD Coated with Lac Gum (50%Encapsulation)

500 g of freeze-dried superoxydismutase enzyme (SOD) were weighted andput into a fluid bed (GPCG1, GLATT) and fluidized. 516 g of Lac gum (ie:500 g of Dry Lac gum) were dissolved at 27% dry matter in water andsprayed on the fluidized SOD. Process temperature of the powder did notexceed 39° C. Final product had a moisture content of 3.4% and anaverage particle size mean of 470 μm (Median diameter Dv(0.5) measuredby laser particle sizer Malvern).

Analyses of SOD activity were made in water solution at pH 2.9 and 7.0.

Less than 5% SOD activity was observed at pH 2.9 although more than 94%of SOD activ is recovered at pH 7.0.

Example 13 Microcapsules Containing SOD Coated with Lac Gum (50%Encapsulation)

500 g of freeze-dried of superoxydismutase enzyme (SOD) were weightedand put into a fluid. bed (GPCG1, GLATT) and fluidized. 516 g of Lac gum(ie: 500 g of Dry Lac gum) were dissolved at 10% dry matter in ethanoland sprayed on the fluidized SOD. Process temperature of the powder didnot exceed 36° C. Final product had a moisture content of 1.9% and anaverage particle size mean of 330 μm (Median diameter Dv(0.5) measuredby laser particle sizer Malvern).

Analyses of SOD activity were made in water solution at pH 2.9 and 7.0.

No SOD activity was observed at pH 2.9 although more than 94% of SODactivityis recovered at pH 7.0.

Example 14 Microcapsules Containing SOD Coated with Lac Gum (30%Encapsulation

490 g of freeze-dried superoxydismutase enzyme (SOD) of enzyme activityof 81.6 U/mg were weighted and put in a fluid bed (GPCG1, GLATT) andfluidized. 216 g of Lac gum (ie: 210 g of dry Lac gum) were dissolve at20% dry matter in ethanol and sprayed on the fluidized SOD. Processtemperature do not exceed 40° C.

Final product has a moisture content of 2.8% and an average particlesize of 250 (Median diameter Dv(0.5) measured by laser particle sizerMalvern).

Analysis of SOD made in a solution of 230 mg of the final product in 30g of water at pH 4.0 and room temperature, gives a measurement of SODactivity in the solution of less than 1 U/mg in the solution after 15 mn(less than 2% of the SOD encapsulated in the microcapsule).

The same measurement made in a solution containing 230 mg of the finalproduct in 30 g of tap water at ph 7.0 and room temperature, gives ameasurement of SOD activity in the solution of 44 tiling in the solutionafter 15 mn (ie: 77% of the SOD encapsulated in the microcapsule).

Example 15 Microcapsules Containing SOD Coated with Lac Gum (50%Encapsulation)

500 g of freeze-dried superoxydismutase enzyme (SOD) were weighted andput in a fluid bed (GPCG1, GLATT) and fluidized, 516 g of Lac gum (ie:500 g of dry Lac gum) were dissolve at 20% dry matter in ethanol andsprayed on the fluidized SOD. Process temperature does not exceed 36° C.

Final product has a moisture content of 2.5% and an average particlesize of 210 μm (Median diameter Dv(0.5) measured by laser particle sizerMalvern).

Analysis of SOD made in a solution of 230 mg of the final product in 30g of water at pH 4.0 and room temperature, gives a measurement of SODactivity in the solution of less than 2 U/mg in the solution after 15 mn(less than 4% of the SOD encapsulated in the microcapsule).

The same measurement made in a solution containing 230 mg of the finalproduct in 30 g of tap water at ph 7.0 and room temperature, gives ameasurement of SOD activity in the solution of 23 U/mg in the solutionafter 15 mn (ie: 58% of the SOD encapsulated in the microcapsule).

Example 16 Microcapsules Containing SOD Coated with Lac Gum (30%Encapsulation)

400 g of spray-dried superoxydismutase enzyme (SOD) were weiahted andput into a fluid bed (GPCG1, GLATT) and fluidized. 176 g of Lac gum (ie:171 g of Dry Lac gum) were dissolved at 10% dry matter in ethanol andsprayed on the fluidized SOD. Process temperature of the powder did notexceed 34° C. Final product had a moisture content of 2.8% and anaverage particle size mean of 320 μm (Median diameter Dv(0.5) measuredby laser particle sizer Malvern).

Analyses of SOD activity were made in water solution at pH 2.9 and 7.0.

Less than 3% SOD activity was observed at pH 2.9 although more than 89%of SOD activity was recovered at pH 7.0.

Example 17 Composition for Food Supplement use

317 g of microcapsules of example 16 were mixed to 685 g ofmaltodextrins to obtain a composition of 14 UI /mg. 60 mg of thiscomposition was then packed into gelatin capsules for food supplementuse.

Example 18 Microcapsules Containing SOD Coated with Lac Gum (50%Encapsulation)

500 g of spray-dried superoxydismutase enzyme (SOD) were weighted andput into a fluid bed (GPCG1, GLATT) and fluidized. 516 g of Lac gum (ie:500 g of Dry Lac gum) were dissolved at 27% dry matter in water andsprayed on the fluidized SOD. Process temperature of the powder did notexceed 39° C. Final product had a moisture content of 3.2% and anaverage particle size mean of 450 μm (Median diameter Dv(0.5) measuredby laser particle sizer Malvern).

Analyses of SOD activity were made in water solution at pH 2.9 and 7.0.

Less than 5% SOD activity was observed at pH 2.9 although more than 96%of SOD activity is recovered at pH 7.0,

Example 19 Microcapsules Containing Calcium Ascorbate

1.2 kg of crystalline Calcium Ascorbate were fluidized in a fluid bed(GPCG1 GLATT), inlet air temperature is 70° C.

Then, 1.65 kg of a 5% solution of sodium alginate in dry matter,containing 3 g of ascorbyl palmitate were sprayed on the fluidizedparticles with a bifluid nozzle (spraying system SS 2050), on atop-spray position, as well known by those skilled in the art (inparticular Vandamme et al Miemencapsulation; Tee & Doc; 2007), and thendried. Solid particles are obtained.

Another 480 g of a 5% solution of calcium chloride in dry matter wasthen spray dried on the fluidized particles. Solid particles areobtained A final drying step of 30 nm was then processed at a maximumtemperature of 50° C. on the microcapsules.

The final microcapsules had a moisture content of 1.2% (infraredmeasurement). Particle size distribution was below 500 μm (mean particlesize measured by light diffraction on Malvern sizer) and bulk densitywas of 830 g/l.

Example 20 Microcapsules Containing SOD Coated with Lac Gum

500 g of freeze-dried superoxydismutase enzyme (SOD) were weighted andput into a fluid bed (GPCG1, GLATT) and fluidized. 516 g of Lac gum (ie:500 g of Dry Lac gum) were solubilized and sprayed on the fluidized SOD.Process temperature of the powder did not exceed 35° C. Final producthad a moisture content of 2.1% and an average particle size mean of 210μm (Median diameter Dv(0.5) measured by laser particle sizer Malvern).

Analyses of SOD activ were made in water solution at pH 2.9 and 7.0.

Less than 1% SOD activity was observed at pH 2.9 although more than 95%of SOD activity was recovered at pH 7.0 after 1H

Example 21 Preparation of a Beverage Composition ComprisingMicrocapsules

Containing SOD Coated with Lac Gum and Orange Juice

40 mg of microcapsules obtained in example 20 were added to a servingbottle of 100 ml of orange fruit juice, at pH=3.7. The mix was shaken 10sec (usual time needed before drinking such a beverage) and then SODactivity was measured. No SOD activity was founded in the juice, meaningthat no SOD was released in the fruit juice during the preparation ofthe beverage with SOD.

Example 22 Pulverulent Composition for the Preparation of an InstantDrink

10 mg of microcapsules of example 20 were mixed with the followingpowders: 0.2 g of xanthan gum, 0.8 g of glucose syrup DE38, and 1 g ofsucrose. The whole mix was packed in a stick. The stick was added to 100ml of mineral water pH=6.9, and stirred gently during 10 sec. Analysisof the SOD activity in the solution after 15 mn was less than 3% of thetotal activity of the 10 mg of SOD showing that almost no release of SODappeared during the preparation of such an instant drink. The timerelease of the SOD is long enough to allow ingestion of almost the wholeSOD activity given.

Example 23 Preparation of a Beverage Composition ComprisingMicrocapsules Containing SOD Coated with Lac Gum and Apple Juice

1.2 g of microcapsules of example 20 were added to 10 L of freshlypressed apple juice pH=3.9 and dispersed and stirred in the juice during1 mn. These 10 L of preparation were pasteurized at 70° C. during 15 secand then packed in closed bottles, and cooled to less than 30° C. in10mn. Analysis of the SOD activity in the apple juice was made after 1day and 1 month. No SOD activity was founded in the juice. Analysis weremade neutralizing the juice to pH 7.5; more than 50% of the totalactivity of the SOD was recovered when extractina the SOD from themicrocapsules in the apple juice at neutral pH showing that no releaseof SOD occurred in this acid fruit juice drinks.

Example 24 Preparation of a Beverage Composition ComprisingMicrocapsules Containing SOD Coated with Lac Gum and a LiquidUnfermented Product

40 mg of microcapsules of example 20 were added to 100 ml of a liquidunfermented dairy product pH 4.4 and shake during 5 sec. Analysis of theSOD activity in the dairy beverage was less than 2% of the totalactivity of the 40 mg of SOD showing that almost no release of SODappeared during the preparation of such an instant drink.

Example 25 Microcapsules Containing Oxidizable Oil

349 g of tocopherol acetate was mixed with 160 g of modified starch, 247g of maltodextrin, 40 g of alginate and 1.22 kg of water.

The preparation was homogenized at 200 bars.

Another 8 g of a calcium chloride aqueous solution at 5% dry matte asprepared.

The homogenized preparation was then sprayed in a single stage dryer(Minor production tower, GEA-NIRO) combined with the calcium chloridesolution as a mean for insolubility with a trifluid nozzle. Drying wasmade with an inlet temperature of 120° C. and outlet temperature of 70°C.

The final microcapsules are insoluble and have a mean particle size of80 nm (mean particle size measured by light diffraction on Malvernsizer), a moisture content of 3.2% and a bulk density of 470 g/l.

1. Microcapsule consisting of or comprising: a core consisting of orcomprising an oxidizable active (OA), the outer part of said core beingin a solid form; and a water insoluble coating obtained from anencapsulating agent (EA), said coating surrounding said core, inparticular, a microcapsule wherein said EA is water soluble or organicsolvent, in particular ethanol, soluble, or a microcapsule wherein saidEA is an agent, the water solubility of which is pH-dependent, whereinsaid OA is selected from the group consisting of vitamin C, vitamin B5,vitamin B6, vitamin B8, vitamin B9, vitamin A, vitamin D3, vitamin K andvitamin E, with the proviso that: said core does not comprise a metaloxide, and said coating does not comprise a disintegrant, in particularsodium starch glycolate.
 2. The microcapsule according to claim 1,wherein said water insoluble coating results from the reaction of awater soluble or organic solvent, in particular ethanol, soluble EA withmeans for inducing water insolubility of said EA, in particular: amicrocapsule wherein said means for inducing water insolubility are anagent chemically reacting with said EA; or a microcapsule wherein saidmeans for inducing water insolubility are an acid, a base, or a buffer;or a microcapsule wherein said means for inducing water insolubilityconsist in the drying of said EA.
 3. The microcapsule according to claim1, wherein said coating is such that, when said microcapsule is placedin an alimentary, cosmetically or pharmaceutically acceptable medium:said OA is not degraded by element(s) of said medium; and saidelement(s) of the medium is (are) not degraded by said OA.
 4. Themicrocapsule according to claim 1, wherein the mass of said coating iswithin the range of from 3 to 50%, preferably from 4 to 12%, morepreferably from 5 to 8%, of the total mass of said microcapsule.
 5. Themicrocapsule according to claim 1, wherein said microcapsule size is inthe range of from 1 mn to 3 mm, preferably from 20 to 500 nm, morepreferably from 50 to 200 nm.
 6. The microcapsule according to claim 1,wherein said OA is: in a crystalline state, in particular a microcapsulewherein said core consists in or comprises an OA in a crystalline stateand at least one additional element selected among drying agents,antioxidant agents, filmogen agents and emulsifying agents; or in anamorphous state, in particular a microcapsule wherein said core consistsin or comprises an OA in an amorphous state and at least one additionalelement selected among drying agents, antioxidant agents, fihnogenagents and emulsifying agents.
 7. The microcapsule according to claim 1,wherein said water soluble EA is selected from alginates of monovalentcations, in particular Na⁺ alginates and K⁺ alginates, in particularwherein said EA is water soluble and selected from alginates ofmonovalent cations, more particularly Na⁺ alginates and K⁺ alginates,and wherein said means for inducing water insolubility are a saltwherein the cation is a divalent metallic cation, more particularly Ca²⁺or Mg²⁺, said salt being in particular CaCl₂ or MgCl₂.
 8. Themicrocapsule according to claim 1, wherein said water soluble or organicsolvent, in particular ethanol, soluble EA is lac gum, said means forinducing water insolubility consisting in particular in the drying ofsaid lac gum, or are an acid, in particular ascorbic acid, citric acid,acetic acid or hydrochloric acid.
 9. The microcapsule according to claim1, wherein said OA: is vitamin C, in particular natural vitamin C,synthetic vitamin C, or salts of U. ascorbic acid, more particularlysodium L-ascorbate, calcium L-ascorbate and iron L-ascorbate, orcomprises vitamin C, said OA being in particular a fruit juicecomprising vitamin C, in particular orange juice, kiwi juice, cranberryjuice, acerola juice or goji juice, said fruit juice being optionallyconcentrated or dried.
 10. The microcapsule according to claim 1,wherein said OA is vitamin C or comprises vitamin C and wherein said EAis water soluble and selected from alginates of monovalent cations, inparticular Na⁺ alginates and K⁺ alginates, in particular a microcapsulewherein said OA is vitamin C or comprised vitamin C, wherein said EA iswater soluble and selected from alginates of monovalent cations, inparticular Na⁺ alginates and K⁺ alginates, and wherein said means forinducing water insolubility are a salt wherein the cation is a divalentmetallic cation, in particular Ca²⁺ or Mg⁺, said salt being inparticular CaCl₂ or MgCl₂.
 11. Process of preparation of themicrocapsules of claim 1, comprising the following steps: spray-drying aliquid mixture consisting of or comprising: said OA; optionally said EA;optionally at least one additional element selected among drying agents,antioxidant agents, filmogen agents and emulsifying agents, to obtainparticles consisting of said OA, or particles comprising said OA, saidEA and/or at least one additional element, the outer part of saidparticles being in a solid form, spraying on said particles an insolubleEA or means for inducing water insolubility of EA comprised in saidparticle, to obtain microcapsules with a water insoluble coating, saidwater insoluble coating surrounding a core consisting of said OA, orcomprising said OA, said EA and/or at least one additional element, withthe proviso that: said core does not comprise a metal oxide, and saidcoating does not comprise a disintegrant, in particular sodium starchglycolate.
 12. The process according to claim 11 comprising, after saidspray-drying and spraying steps, a step of drying said microcapsules toobtain dried microcapsules, said spray-drying step, spraying step anddrying step being in particular done in a spray-dryer.
 13. The processaccording to claim 11, comprising the following steps: spray-drying aliquid mixture consisting of or comprising: said OA; and optionally atleast one additional element selected among drying agents, antioxidantagents, filmogen agents and emulsifying agents, to obtain particlesconsisting of said OA, or particles comprising said OA and said at leastone additional element, spraying on said particles a water insoluble EA,to obtain microcapsules with a water insoluble coating, said waterinsoluble coating surrounding a core consisting of said OA, orcomprising said OA and said at least one additional element.
 14. Theprocess according to claim 11, comprising the following steps:spray-drying a liquid mixture consisting of or comprising: said OA; awater soluble EA; and optionally at least one additional elementselected among drying agents, antioxidant agents, filmogen agents andemulsifying agents, to obtain particles comprising said OA, said EA andoptionally said at least one additional element, spraying on saidparticles means for inducing water insolubility of EA comprised in saidparticle, to obtain microcapsules with a water insoluble coating, saidwater insoluble coating surrounding a core comprising said OA, said EAand optionally at least one additional element; or comprising a step ofco-spraying in a spray-dryer: a liquid mixture consisting of orcomprising: said OA; and a water soluble EA; optionally at least oneadditional element selected among drying agents, antioxidant agents,filmogen agents and emulsifying agents; and means for inducing waterinsolubility of said EA, to obtain microcapsules with a water insolublecoating, said water insoluble coating surrounding a core comprising saidOA, said EA and optionally at least one additional element, saidco-spraying being performed with two separate means of pulverization, inparticular two separate nozzles, or with two combined means ofpulverization, in particular a trifluid nozzle.
 15. The processaccording to claim 11, comprising a step of spraying on particlesconsisting of said OA, or particles comprising said OA, said EA and/orat least one additional element selected among drying agents,antioxidant agents, filmogen agents and emulsifying agents, an insolubleEA or means for inducing water insolubility of EA comprised in saidparticle, to obtain microcapsules with a water insoluble coating, saidwater insoluble coating surrounding a core consisting of said GA, orcomprising said OA said EA and/or at least one additional element, saidprocess comprising in particular a step of spraying on particlesconsisting of said OA, or particles comprising said OA and at least oneadditional element selected among drying agents, antioxidant agents,tilmogen agents and emulsifying agents, a water insoluble coating toobtain microcapsules with a water insoluble coating, said waterinsoluble coating surrounding a core consisting of said OA, orcomprising said OA, and said at least one additional element.
 16. Theprocess according to claim 15, comprising in a device a step of sprayingon particles comprising: said OA, a water soluble EA, and optionally atleast one additional element selected among drying agents, antioxidantagents, filmogen agents and emulsifying agents, means for inducing waterinsolubility of EA comprised in said particle, to obtain microcapsuleswith a water insoluble coating, said water insoluble coating surroundinga core comprising said OA, and said EA and/or at least one additionalelement, in particular: a process wherein said particles are obtained bycoating said OA in a solid state with said water soluble EA andoptionally at least one additional element selected among drying agents,antioxidant agents, filmogen agents and emulsifying agents, or a processwherein said particles are obtained in a spray-dryer by co-spraying ahomogenous aqueous solution comprising: said water soluble EA,optionally at least one additional element selected among drying agents,antioxidant agents, filmogen agents and emulsifying agents; and said OAin a solid state, said spraying of said means for inducing waterinsolubility of EA being in particular performed in the spray-dryer usedto obtain said particles.
 17. A process of preparation of themicrocapsules of claim 1, comprising the following steps: spraying, onparticles consisting of said OA, or particles comprising said OA and atleast one additional element selected among drying agents, antioxidantagents, filmogen agents and emulsifying agents, a water soluble ororganic solvent, in particular ethanol, soluble EA to obtain particlessurrounded by said EA; and drying said particles surrounded by said EA,to obtain microcapsules with a water insoluble coating, said waterinsoluble coating surrounding a core comprising said OA, and optionallyat least one additional element, said water soluble or organicsolvent-soluble EA being in particular lac gum, said lac gum being inparticular dissolved in water or ethanol, said spraying step and dryingstep being in particular done in a spray-dryer.
 18. A process ofpreparation of the microcapsules of claim 1, comprising the followingsteps: spray-drying a liquid mixture consisting of or comprising: saidOA; and optionally at least one additional element selected among dryingagents, antioxidant agents, filmogen agents and emulsifying agents; toobtain spray-dried particles consisting in said OA, or particlescomprising said OA and at least one additional element, spraying on saidparticles a water soluble or organic solvent, in particular ethanol,soluble EA, to obtain particles surrounded by said EA; and drying saidparticles surrounded by said EA, to obtain microcapsules with a waterinsoluble coating, said water insoluble coating surrounding a corecomprising said OA, and optionally at least one additional element, saidwater soluble or organic solvent-soluble EA being in particular lac gum,said be gum being in particular dissolved in water or ethanol, saidspray-drying step, spraying step and drying step being in particulardone in a spray-dryer.